1k06: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1k06.gif|left|200px]] | [[Image:1k06.gif|left|200px]] | ||
'''Crystallographic Binding Study of 100 mM N-benzoyl-N'-beta-D-glucopyranosyl urea to glycogen phosphorylase b''' | {{Structure | ||
|PDB= 1k06 |SIZE=350|CAPTION= <scene name='initialview01'>1k06</scene>, resolution 1.80Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=BZD:N-BENZOYL-N'-BETA-D-GLUCOPYRANOSYL+UREA'>BZD</scene> and <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] | |||
|GENE= | |||
}} | |||
'''Crystallographic Binding Study of 100 mM N-benzoyl-N'-beta-D-glucopyranosyl urea to glycogen phosphorylase b''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
1K06 is a [ | 1K06 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K06 OCA]. | ||
==Reference== | ==Reference== | ||
Binding of N-acetyl-N '-beta-D-glucopyranosyl urea and N-benzoyl-N '-beta-D-glucopyranosyl urea to glycogen phosphorylase b: kinetic and crystallographic studies., Oikonomakos NG, Kosmopoulou M, Zographos SE, Leonidas DD, Chrysina ED, Somsak L, Nagy V, Praly JP, Docsa T, Toth B, Gergely P, Eur J Biochem. 2002 Mar;269(6):1684-96. PMID:[http:// | Binding of N-acetyl-N '-beta-D-glucopyranosyl urea and N-benzoyl-N '-beta-D-glucopyranosyl urea to glycogen phosphorylase b: kinetic and crystallographic studies., Oikonomakos NG, Kosmopoulou M, Zographos SE, Leonidas DD, Chrysina ED, Somsak L, Nagy V, Praly JP, Docsa T, Toth B, Gergely P, Eur J Biochem. 2002 Mar;269(6):1684-96. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11895439 11895439] | ||
[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Phosphorylase]] | [[Category: Phosphorylase]] | ||
| Line 32: | Line 41: | ||
[[Category: structure]] | [[Category: structure]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:10:47 2008'' | ||
Revision as of 13:10, 20 March 2008
| |||||||
| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Phosphorylase, with EC number 2.4.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystallographic Binding Study of 100 mM N-benzoyl-N'-beta-D-glucopyranosyl urea to glycogen phosphorylase b
OverviewOverview
Two substituted ureas of beta-D-glucose, N-acetyl-N'-beta-D-glucopyranosyl urea (Acurea) and N-benzoyl-N'-beta-D-glucopyranosyl urea (Bzurea), have been identified as inhibitors of glycogen phosphorylase, a potential target for therapeutic intervention in type 2 diabetes. To elucidate the structural basis of inhibition, we determined the structure of muscle glycogen phosphorylase b (GPb) complexed with the two compounds at 2.0 A and 1.8 A resolution, respectively. The structure of the GPb-Acurea complex reveals that the inhibitor can be accommodated in the catalytic site of T-state GPb with very little change in the tertiary structure. The glucopyranose moiety makes the standard hydrogen bonds and van der Waals contacts as observed in the GPb-glucose complex, while the acetyl urea moiety is in a favourable electrostatic environment and makes additional polar contacts with the protein. The structure of the GPb-Bzurea complex shows that Bzurea binds tightly at the catalytic site and induces substantial conformational changes in the vicinity of the catalytic site. In particular, the loop of the polypeptide chain containing residues 282-287 shifts 1.3-3.7 A (Calpha atoms) to accommodate Bzurea. Bzurea can also occupy the new allosteric site, some 33 A from the catalytic site, which is currently the target for the design of antidiabetic drugs.
About this StructureAbout this Structure
1K06 is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
ReferenceReference
Binding of N-acetyl-N '-beta-D-glucopyranosyl urea and N-benzoyl-N '-beta-D-glucopyranosyl urea to glycogen phosphorylase b: kinetic and crystallographic studies., Oikonomakos NG, Kosmopoulou M, Zographos SE, Leonidas DD, Chrysina ED, Somsak L, Nagy V, Praly JP, Docsa T, Toth B, Gergely P, Eur J Biochem. 2002 Mar;269(6):1684-96. PMID:11895439
Page seeded by OCA on Thu Mar 20 12:10:47 2008